60252-41-7Relevant articles and documents
Catalytic Asymmetric Synthesis of Unprotected β2-Amino Acids
Zhu, Chendan,Mandrelli, Francesca,Zhou, Hui,Maji, Rajat,List, Benjamin
, p. 3312 - 3317 (2021/04/07)
We report here a scalable, catalytic one-pot approach to enantiopure and unmodified β2-amino acids. A newly developed confined imidodiphosphorimidate (IDPi) catalyzes a broadly applicable reaction of diverse bis-silyl ketene acetals with a silylated aminomethyl ether, followed by hydrolytic workup, to give free β2-amino acids in high yields, purity, and enantioselectivity. Importantly, both aromatic and aliphatic β2-amino acids can be obtained using this method. Mechanistic studies are consistent with the aminomethylation to proceed via silylium-based asymmetric counteranion-directed catalysis (Si-ACDC) and a transition state to explain the enantioselectivity is suggested on the basis of density functional theory calculation.
Method for preparing (S)-3-piperidinecarboxylic acid
-
Paragraph 0025-0030; 0036; 0039; 0041, (2017/08/29)
The invention discloses a method for preparing (S)-3-piperidinecarboxylic acid. The method includes steps of carrying out reaction on 3-piperidinecarboxamide or salt of the 3-piperidinecarboxamide in concentrated hydrochloric acid to obtain (S)-3-piperidinecarboxylic acid salt; converting the (S)-3-piperidinecarboxylic acid salt to obtain the (S)-3-piperidinecarboxylic acid. The method has the advantages that the reaction is carried out on the 3-piperidinecarboxamide or the salt of the 3-piperidinecarboxamide in the concentrated hydrochloric acid, accordingly, chiral resolution effects can be realized while hydrolysis is carried out, and resolution on the 3-piperidinecarboxamide or 3-piperidinecarboxylic acid by the aid of chiral resolving agents can be omitted; preparation processes are simple in post-treatment operation, N protection and de-protection processes are omitted, accordingly, the method is high in atomic economy and low in cost, and a simple, feasible and low-cost production method can be provided for synthesizing the (S)-3-piperidinecarboxylic acid.
Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2)
Futatsugi, Kentaro,Kung, Daniel W.,Orr, Suvi T. M.,Cabral, Shawn,Hepworth, David,Aspnes, Gary,Bader, Scott,Bian, Jianwei,Boehm, Markus,Carpino, Philip A.,Coffey, Steven B.,Dowling, Matthew S.,Herr, Michael,Jiao, Wenhua,Lavergne, Sophie Y.,Li, Qifang,Clark, Ronald W.,Erion, Derek M.,Kou, Kou,Lee, Kyuha,Pabst, Brandon A.,Perez, Sylvie M.,Purkal, Julie,Jorgensen, Csilla C.,Goosen, Theunis C.,Gosset, James R.,Niosi, Mark,Pettersen, John C.,Pfefferkorn, Jeffrey A.,Ahn, Kay,Goodwin, Bryan
supporting information, p. 7173 - 7185 (2015/10/05)
The medicinal chemistry and preclinical biology of imidazopyridine-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) is described. A screening hit 1 with low lipophilic efficiency (LipE) was optimized through two key structural modifications: (1) identification of the pyrrolidine amide group for a significant LipE improvement, and (2) insertion of a sp3-hybridized carbon center in the core of the molecule for simultaneous improvement of N-glucuronidation metabolic liability and off-target pharmacology. The preclinical candidate 9 (PF-06424439) demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models.
Characterization of an enantioselective amidase from Cupriavidus sp. KNK-J915 (FERM BP-10739) useful for enzymatic resolution of racemic 3-piperidinecarboxamide
Nojiri, Masutoshi,Taoka, Naoaki,Yasohara, Yoshihiko
, p. 136 - 142 (2014/12/10)
A novel amidase (CsAM) acting on (R,S)-N-benzyl-3-piperidinecarboxamide was purified from Cupriavidus sp. KNK-J915 (FERM BP-10739) and characterized. The enzyme acts on (R,S)-N-benzyl-3-piperidinecarboxamide S-selectively to yield (R)-N-benzyl-3-piperidinecarboxamide. Analytical gel filtration column chromatography and SDS-PAGE revealed that the enzyme is a tetramer with a subunit of approximately 47 kDa. It has a broad substrate spectrum against nitrogen-containing heterocyclic amides. Its optimal pH and temperature are 8.0-9.0 and 50 °C, respectively. The CsAM gene was cloned and sequenced, and it was found to comprise 1341 bp and encode a polypeptide of 46,388 Da. The deduced amino acid sequence exhibited 78% identity to that of a putative amidase (CnAM) from Cupriavidus necator JMP134. The cultured cells of recombinant Escherichia coli producing CnAM could be used for the S-selective hydrolysis of (R,S)-N-benzyl-3-piperidinecarboxamide but could not be used for the S-selective hydrolysis of (R,S)-3-piperidinecarboxamide because of its very low level of selectivity. In contrast, the cultured cells of recombinant E. coli producing CsAM could hydrolyze both (R,S)-N-benzyl-3-piperidinecarboxamide and (R,S)-3-piperidinecarboxamide with high S-selectivity.
PROCESS FOR PRODUCING SOLID AMINO ACID
-
Paragraph 0057-0060, (2014/12/09)
The problem to be solved by the present invention is to ea lily and efficiently produce an amino acid having 2 to 7 carbon atoms as a high-purity solid without complicated operation, which is useful as a synthetic intermediate for medicines or agrochemicals. The present invention is characterized in comprising a step of precipitating solid amino acid with high purity. In the present invention, the by-produced salt composed of the sulfonic acid and the amine was removed to the mother liquor by reacting an amine with a sulfonic acid salt of amino acid in an aprotic polar solvent, or by reacting a sulfonic acid with an amine salt of amino acid in an aprotic polar solvent. The sulfonic acid salt of amino acid, for example, may be produced by reacting a N-(tert-butoxycarbonyl) amino acid with a sulfonic acid, or by reacting an amino acid tert-butyl ester with a sulfonic acid.
DIACYLGLYCEROL ACYLTRANSFERASE 2 INHIBITORS
-
Page/Page column 138, (2013/10/22)
Derivatives of purine, 3H-imidazo[4,5-b]pyrimidine and 1H- imidazo[4,5-d]pyrazine of Formula I that inhibit the activity of the diacylglycerol acyltransferase 2 (DGAT2) and their uses in the treatment of diseases linked thereto in animals are described herein.
Iridium-catalyzed enantioselective hydrogenation of unsaturated heterocyclic acids
Song, Song,Zhu, Shou-Fei,Pu, Liu-Yang,Zhou, Qi-Lin
, p. 6072 - 6075 (2013/07/05)
Spiral binding: A highly enantioselective hydrogenation of unsaturated heterocyclic acids has been developed by using chiral iridium/spirophosphino oxazoline catalysts (see scheme; BArF-=tetrakis[3,5- bis(trifluoromethyl)phenyl]borate, Boc=tert-butoxycarbonyl). This reaction provided an efficient method for the preparation of optically active heterocyclic acids with excellent enantioselectivities. Copyright
METHOD FOR PRODUCING OPTICALLY ACTIVE 3-AMINOPIPERIDINE OR SALT THEREOF
-
Page/Page column 15-16, (2010/05/13)
The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing.
Preparation of β2-amino acid derivatives (β2hThr, β2hTrp, β2hMet, β2hPro, β2hLys, pyrrolidine-3-carboxylic acid) by using DIOZ as chiral auxiliary
Gessier, Francois,Schaeffer, Laurent,Kimmerlin, Thierry,Floegel, Oliver,Seebach, Dieter
, p. 2235 - 2249 (2007/10/03)
The title compounds were prepared from valine-derived N-acylated oxazolidin-2-ones, 1-3, 7, 9, by highly diastereoselective (≥ 90%) Mannich reaction (→ 4-6; Scheme 1) or aldol addition (→ 8 and 10; Scheme 2) of the corresponding Ti- or B-enolates as the key step. The superiority of the '5,5-diphenyl-4-isopropyl-1,3-oxazolidin-2-one' (DIOZ) was demonstrated, once more, in these reactions and in subsequent transformations leading to various t-Bu-, Boc-, Fmoc-, and Cbz-protected β2-homoamino acid derivatives 11-23 (Schemes 3-6). The use of ω-bromo-acyl-oxazolidinones 1-3 as starting materials turned out to open access to a variety of enantiomerically pure trifunctional and cyclic carboxylic-acid derivatives.
Stereochemical control of hairpin formation in β-peptides containing dinipecotic acid reverse turn segments
Chung, Yong Jun,Huck, Bayard R.,Christianson, Laurie A.,Stanger, Heather E.,Krauthaeuser, Susanne,Powell, Douglas R.,Gellman, Samuel H.
, p. 3995 - 4004 (2007/10/03)
We examine the relationship between covalent structure and conformational propensity among a series of β-amino acid tetramers. These experiments focus on the hairpin folding motif. Among conventional peptides, the minimum increment of β-sheet secondary structure is a 'β-hairpin,' in which two strands are connected via a short loop. The present studies are aimed at optimizing hairpin stability among β-peptides. Previous work from our laboratory has identified optimal substitution patterns for residues that form strands in an antiparallel β-peptide sheet (Krauthauser et al. J. Am. Chem. Soc. 1997, 119, 11719), and we have shown that a dinipecotic acid segment can promote sheet-type interactions between attached strand residues (Chung et al. J. Am. Chem. Soc. 1998, 120, 10555). Here we compare all four possible configurations of the dinipecotic acid segment, (R,S), (S,R), (R,R) and (S,S), for the ability to induce sheet formation with a constant set of enantiomerically pure strand residues. We show that both heterochiral dinipecotic acid segments promote hairpin formation, although one is distinctly superior. Neither of the homochiral dinipecotic acid supports hairpin folding. When the strand residues are β-alanine (achiral), the heterochiral dinipecotic acid segment is again superior to the homochiral segment, but we find a difference between hairpin conformations in solution and in the solid state.
